This research will investigate the effects of an environmental treatment (environmental enrichment), for preventing the negative emotional and cardiovascular consequences of social isolation in the context of depression and heart disease. There is a bidirectional association between depression and heart disease, and this relationship is especially important for people with specific vulnerabilities such as aging populations or individuals who lack beneficial social experiences. Psychological and physiological responses to social stressors and isolation play an important role in the development of affective symptoms and cardiovascular dysfunction. However, current treatments for individuals with depression and heart disease are significantly limited. The present project will use a rodent model, the socially monogamous prairie vole, to study behavioral, autonomic responses to a social stressor (social isolation), and potential molecular mechanisms that underlie environmental enrichment as a treatment for these negative consequences. Preliminary findings, from our laboratory and others, indicate that environmental enrichment - involving increased stimulation from the environment in the form of inanimate objects and physical activity - has beneficial effects on several central nervous system functions, and can improve emotional reactivity and behaviors associated with depression. The prairie vole is a valuable model system for studying responsiveness to social experiences and neurobiological mechanisms related to mood and cardiovascular function. This species displays several unique social behaviors that mimic those of humans, including living in extended families and forming enduring social bonds; and also exhibits autonomic regulation of the heart similar to humans. Using the prairie vole model, Specific Aim 1 will employ behavioral tests of depression and continuous recording of cardiovascular variables including blood pressure, heart rate, heart rate variability, and autonomic balance, to test the hypothesis that environmental enrichment is an effective treatment for behavioral and cardiovascular consequences of social isolation. Specific Aim 2 will employ measures of central nervous system genes including delta-FosB immunoreactivity, to investigate the hypothesis that long-term alterations in cortical, limbic, and autonomic brain regions underlie the positive effects of environmental enrichment in animals that are socially isolated. This research proposes a novel mechanism by which the social environment impacts behavior, physiology, and brain function, and will promote the development of more comprehensive treatments for patients with depression and cardiovascular disease. PUBLIC HEALTH RELEVANCE: The association between depression and heart disease is bidirectional, and is significantly influenced by the social environment. The current research project will investigate, in an animal model, the ability of an environmental treatment to protect against negative behavioral, cardiovascular, and brain processes associated with mood and cardiovascular dysfunction. This research will lead to the development of more effective treatments for patients with depression and heart disease.